Formulation process

ABSTRACT

A process of preparing a herbicidal emulsion comprising 75 grams per liter or more of a salt of a herbicidal bipyridylium diquaternary cation as an active ingredient comprising as a first step agitating an aqueous solution of a herbicidal bipyridylium diquaternary salt with an oil and a first emulsifier having a low HLB value to give a first emulsion comprising droplets of herbicidal bipyridylium diquaternary salt solution dispersed in a continuous oil phase, and as a second step, agitating the first emulsion with water and a second emulsifier having a high HLB value, to give a second emulsion comprising drops of the first emulsion dispersed in a continuous aqueous phase. The emulsions have a lower oral toxicity than conventional aqueous formulations.

This invention relates to methods of preparing herbicidal compositionscomprising a multiple emulsion containing a bipyridylium diquaternarysalt as the active ingredient.

Various herbicidal bipyridylium diquaternary salts are described in U.K.Patent Specification Nos. 785732, 813531 and 813532. Certain of thesecompounds are in widespread use in agriculture, and are manufactured forsale in the form of concentrated aqueous solutions. When required foruse, these concentrated solutions are diluted with water to form asolution which is then sprayed upon unwanted plants. When used with duecare, and in accordance with recommended procedures, the concentratedaqueous solutions present no hazard. However, hazards may develop ifadherence to the recommended handling practices is not maintained. Thusit may happen that an operator may decant some of the concentrate into adomestic container such as a beverage bottle for subsequent use in hisown garden at home. The hazard associated with such a practice is ofcourse that a child or incautious adult coming upon the bottle mayswallow some of the contents, with possible serious consequences.

Various methods have been proposed to reduce the likelihood ofaccidental swallowing of concentrated solutions of bipyridyliumdiquaternary salts in the circumstances described above. These includethe inclusion of an odourant in the concentrate as a warning (see U.K.Pat. Nos. 1406881 and 1570981) and the addition of a gelling agent (seeU.K. Pat. No. 1395502). Another approach has been to include an emeticin the concentrate, so that the concentrate will be regurgitated shortlyafter its ingestion (See U.K. Pat. No. 1507407). In addition to methodsof formulating bipyridylium herbicides so as to reduce the likelihood ofaccidental ingestion, a variety of methods has been proposed forformulating bipyridylium herbicides so as to improve their suitabilityfor particular applications. Thus, it has been proposed to formulate anaqueous solution of paraquat as an invert emulsion in oil (see U.S. Pat.No. 4,115,098) in order to reduce drift and evaporation of the dropletsof spray when the paraquat is applied as a herbicide.

A method of formulating herbicidal bipyridyllium diquaternary salts as amultiple emulsion has now been devised, whereby the concentrated aqueoussolution of the herbicidal bipyridylium diquaternary salt is emulsifiedin an oil by agitation with a suitable emulsifier, to give an emulsion(the "first emulsion") wherein droplets of the aqueous solution aredispersed through a continuous oil phase. The first emulsion is thenitself dispersed by agitation into an aqueous solution containing asecond emulsifier to give a multiple emulsion (the "second emulsion")which comprises drops of the first emulsion dispersed in a continuousaqueous phase. The drops of the first emulsion themselves containdroplets of the concentrated aqueous solution of the herbicidalbipyridylium salt. The oil surrounding these droplets of aqueousbipyridylium salt solution acts as a barrier and prevents thebipyridylium salt from passing out into the continuous aqueous phase.Preferably, the continuous aqueous phase contains a solute to maintainosmotic balance between this phase and the aqueous solution ofbipyridylium salt. When required for use as a herbicide, the multipleemulsion is diluted and agitated with water. The emulsion then eitherbreaks up and liberates the herbicidal bipyridylium diquaternary saltinto the aqueous spray solution or when the spray solution is applied toweeds the emulsion breaks up or evaporates on the surface of the weedsto liberate the bipyridylium herbicide. However, if a quantity of theconcentrated multiple emulsion formulation is inadvertently swallowed,as a result for example of transfer of the concentrate to a beveragebottle as mentioned above, the volume of fluid in the gastrointestinaltract and the osmotic differential between this fluid and the solutionof the herbidical bipyridylium diquaternary salt are insufficient incombination to break down the multiple emulsion to any substantialextent. The bipyridylium diquaternary salt accordingly remainssubstantially contained in the drops of the emulsion, which passes alongthe gastro-intestinal tract with a substantial reduction in the amountof the bipyridylium diquaternary salt absorbed through the gut wall orinto the bloodstream as compared with the absorption which takes placeas a result of swallowing an aqueous solution of a bipyridyliumdiquaternary salt.

According to the present invention therefore, there is providing aprocess of preparing a herbicidal emulsion comprising 75 grams per literor more of a salt of a herbicidal bipyridylium diquaternary cation as anactive ingredient comprising as a first step agitating an aqueoussolution of a herbicidal bipyridylium diquaternary salt with an oil anda first emulsifier having a low HLB value to give a first emulsioncomprising droplets of herbicidal bipyridylium diquaternary saltsolution dispersed in a continuous oil phase, and as a second step,agitating the first emulsion with water and a second emulsifier having ahigh HLB value, to give a second emulsion comprising drops of the firstemulsion dispersed in a continuous aqueous phase. By low HLB value wemean a value of about 8 or less.

Preferably the continuous aqueous phase contains a solute to bring itinto substantial osmotic balance with the aqueous solution of thebipyridylium diquaternary salt.

The nature of the oil used in the process of the invention is notnarrowly critical and a wide variety of oils may be used. The oil may befor example a vegetable oil, for example soya bean oil, castor oil, orsunflower oil. The oil may also be a mineral oil of comparableviscosity, for example liquid paraffin.

Other oils include white oil, and the oils sold under the trade namesSolvesso, Isopar, and Exsol. The Solvesso oils comprise alkylatedbenzenes. The Isopar oils (eg. Isopar L and Isopar M) compriseisoparaffinic hydrocarbons. The Exsol oils comprise de-aromatisedparaffinic hydrocarbons. Diesel oil may also be used. Commerciallyavailable diesel oil usually contains additives to lower its freezingpoint and to prevent wax separation. These do not appear to affect theuse of the oil in the present invention. The gas oil from whichcommercial diesel oil is prepared is also suitable for use in theprocess of the present invention. Mixtures of oils may be used, forexample mixtures of Isopar M with diesel oil in the ratio of from 1:10to 10:1.

The expession HLB used above is an abbreviation for the termhydrophilic-lipophilic balance. HLB may be defined in terms of anumerical scale, running from 3 to 18 as described by Griffin, J. Soc.Cosmet. Chem 1, 34 (1949) and 5, 249 (1954).

Examples of emulsifiers that can be used as the first emulsifier in theprocess of the invention include an ABA block co-polymer ofpoly-12-hydroxystearic acid and polyethylene oxide. Such co-polymers aredescribed in, for example, published U.K. Patent Application No.2002400. A co-polymer of this kind having a molecular weight of about5000 is referred to in the Example below as Surfactant D.

Another example of an emulsifier is a reaction product ofpolyisobutylenesuccinic anhydride (PIDSA) and ethanolamine, having thegeneral formula below: ##STR1## and an average molecular weight in therange 400-5000, for example 1200. An example of such a polymer isdesignated as Surfactant A in the Example below. Such polymers aredescribed in published U.K. Patent Application No. 2156799 (see forexample page 3 at lines 9-65 and Examples 2 and 3). Other polymers whichmay be used include those described at column 5, line 26 to column 6,line 10 of U.S. Pat. No. 4,244,816. A further example of a firstemulsifier is a related polymer of the above formula which has beenreacted with one mole of phosphoric acid to yield the monophosphatederivative (see Example 5 of U.K. Patent Application No. 2156799). Anemulsifier of this type is referred to as Surfactant B in the Examplebelow.

Other examples of first emulsifiers include the following:

"Span" 80 (sorbitan monooleate)

Mixture of "Span" 809 with "Tween" 20 (sorbitan monolaurate condensedwith 20 molar proportions of ethylene oxide)

"Tween 85" (sorbitan trioleate condensed with 20 molar proportions ofethylene oxide)

Lecithin (phosphatidylcholine)

"Atlox" 1045A (polyoxyethylene sorbitol oleate/laurate)

"Span" 80/lecithin mixtures

"Arlacel" 83 (sorbitan sesquioleate), optionally mixed with lecithin

G 1086 (polyoxyethylene sorbitol hexa-oleate)

Particular examples of mixtures of emulsifiers include mixtures of∓Arlacel" 83 with lecithin, and mixtures of "Arlacel" 83 together withlecithin and Surfactant D referred to above, and mixtures of "Span" and"Tween" surfactants.

Examples of second emulsifiers include the condensate of p-nonylphenolwith propylene oxide and ethylene oxide having the following formula:##STR2## wherein x may be in the range from 2 to 50 or more, and y maybe in the range from 10 to 100 or more.

The emulsifier referred to as Surfactant C in the Example below is acondensate of the last foregoing formula in which x has values rangingfrom 10 to 16 with an average value of 13.5 and y has values rangingfrom 28 to 38 with an average value of 33. Other members of this serieshaving different values for y are referred to below by the code namesshown in the following table.

    ______________________________________                                        Values of y   Name                                                            ______________________________________                                        40-50         Surfactant E                                                    75-85         Surfactant F                                                    170-180       Surfactant G                                                    ______________________________________                                    

Another material useful in preparing the second emulsion is a copolymerof the product referred to above as PIBSA having a molecular weight ofabout 1000, which is copolymerised with methoxypolyethylene glycol in amolar ratio of 1:2. This co-polymer is referred to below as SurfactantH. A further material useful as a second emulsifier comprises a modifiedpolyester with an HLB value of 13 to 15 sold under the code number A109.

Additional second emulsifiers include condensates of para-nonylphenolwith ethylene oxide residues. The product having 20 ethylene oxideresidues is referred to below as Surfactant I and the product with 35ethylene oxide residues is referred to below as Surfactant J.Condensates of C₁₃ to C₁₅ alkanols with from 2 to 50 molar proportionsof ethylene oxide may also be used as second emulsifiers. An example ofthis class containing 30 molar proportions of ethylene oxide is referredto below as Surfactant K. Other examples of second emulsifiers includethose emulsifiers sold under the Trade Names "Pluronic" and "Tween" andpolyvinyl alcohol.

The "Pluronic" emulsifiers are block copolymers of polyethylene oxideand polypropyleneoxide. Particular examples of these include thefollowing:

    ______________________________________                                                     Percentage of                                                                             Molecular                                            Code No.     ethylene oxide                                                                            weight                                               ______________________________________                                        F38          80          4750                                                 L92          20          3438                                                 P65          50          3500                                                 F68          80          8750                                                 F88          80          11250                                                F108         80          16250                                                P94          40          4583                                                 ______________________________________                                    

The "Tween" series of emulsifiers comprises a range of sorbitan esterscondensed with various molar proportions of ethylene oxide. Theseemulsifiers may be used alone or in combination with emulsifiers of thetype of, for example, Surfactant C referred to above.

Other emulsifiers that may be used include the following productsproduced by Rhone-Poulenc:

    ______________________________________                                        Code No.    Chemical composition                                              ______________________________________                                        BSU         Ethoxylated polyarylphenol                                        FL          Ethoxylated polyarylphenol phosphate                                          neutralised with triethanolamine                                  3033        Phosphoric ester of ethoxylated aryl-                                         phenol                                                            40884       Sulphated polyarylphenol ethoxylate                               ______________________________________                                    

In order to improve the stability of the multiple emulsions prepared bythe process of the invention to be stable on storage, it is preferredthat the continuous aqueous phase of the second emulsion is in at leastapproximate osmotic balance with the aqueous solution of herbicidalbipyridylium diquaternary salt used in preparing the emulsions of theinvention. This may conveniently be achieved by including in thecontinuous aqueous phase of the second emulsion a solute which has amolarity with respect to chloride ion similar to that of the anion inthe aqueous solution of the herbicidal bipyridylium diquaternary salt. Aconvenient solute is sodium chloride. Thus, by way of example, anaqueous solution containing 376 grams per liter of paraquat dichlorideis approximately 4.0M with respect to chloride ion. The continuousaqueous phase in the second emulsion should therefore be 4.0 molar withrespect to sodium chloride; that is to say, it should contain 235.75grams (4.0M) of sodium chloride per liter.

At higher concentrations of paraquat, dissociation into paraquat cationand chloride anions may be incomplete and the concentration of thesodium chloride in the continuous aqueous phase may need to be adjustedto compensate for the departure of the osmotic pressure of the paraquatchloride solution from the theoretical value. This means that 1- or2-molar sodium chloride may be sufficient in the above example.Solutions other than sodium chloride solutions may be used as thecontinuous aqueous phase in the compositions of the invention. Thussolutions of other electrolytes (eg. potassium nitrate) ornon-electrolytes (e.g. sucrose) may be employed. However sodium chloridesolutions are particularly convenient since sodium chloride is cheap andreadily available.

The agitation of the aqueous solution of the herbicidal bipyridyliumdiquaternary salt with an oil to form the first emulsion may be carriedout for example by high speed stirring (using for example an Eladostirrer, which operates at speeds for example of up to 25,000revolutions per minute).

The agitation of the first emulsion with the aqueous solution to givethe second emulsion may be carried out for example by low-speed stirringusing a conventional paddle stirrer at very low speeds. Alternatively,high-speed stirring may be used, but if so, it should be used only for avery short time.

Methods of agitating other than those referred to above may be used toprepare the emulsions according to the invention. Thus, the preparationof the first emulsion may be carried out by pressure homogenisation, orby use of ultra-sonic agitation. The preparation of the second emulsionmay be carried out for example by use of static mixers. The period ofagitation required to form the emulsions may vary according to the scaleon which the emulsions are prepared, but may readily be ascertained bysimple trials. Generally, in the preparation of quantities of the orderof 1 to 5 liters, the preparation of the first emulsion by high-speedstirring (eg. using an Elado stirrer) takes from 2 to 10 minutes. Thepreparation of the second emulsion by conventional paddle stirringusually takes from 30 to 60 minutes. If the second emulsion is preparedby high-speed stirring, this may take of the order of 30 seconds.

The multiple emulsions prepared by the process of the invention maycontain further ingredients to improve the retention of the herbicidalbipyridylium diquaternary salt with the drops of the first emulsion forexample, thickeners for the oil phase. An example of such a thickener ispolyisobutene sold, for example, under the trade name Hyvis. A widerange of polyisobutenes may be used, including those having a molecularweight of up to 100,000 or more. Other thickeners include the following:

DC 193 (a polysiloxane polymer)

Lecithin

BM 18 (polyvinyl butyral)

Bentone 34 (a sodium montmorillonite treated with an alkylammonium salt)

Aluminium stearate.

These thickeners may be incorporated at the rate of 10 to 50 grams perliter.

In addition, a coating may be induced around the drops of the firstemulsion. This may be induced by including a gel-forming ingredient inthe emulsions, for example sodium carboxymethyl cellulose. This materialmay be obtained in a range of molecular weights, for example from 44000(grade F20P) to 200,000 (grade F 1000P). Intermediate grades includeF75P (MW 80,000) and F350P (120,000). The carboxymethyl cellulose ispreferably used in conjunction with a salt of a polyvalent cation (e.g.aluminium chloride or sulphate) dissolved in the continuous aqueousphase, so as to produce a coating or film on the drops of the firstemulsion. The strength of the gel coating may be adjusted by addition ofacid (eg. citric acid). Alternatively, the polyvallent cation may beomitted and gel strength adjusted by pH variation only. Another cationwhich may be used in conjunction with sodium carboxymethyl cellulose isan alkyltrimethyl-ammonium cation such as one of thealkyltrimethylammonium chlorides of formula RN(CH₃)⁺ ₃ Cl⁻ (where R isC₁₀ to C₁₈) alkyl) sold under the trade name Arquad. Such a coating orfilm may also be produced by the addition of xanthan gum, used inconjunction with a salt of a polyvalent cation (e.g. ceric chloride) ora borate salt (e.g. sodium borate) dissolved in the continuous aqueousphase.

Other materials which may be used to produce a coating on the drops ofthe first emulsion include sodium polymethylmethacrylate condensed withethylene oxide. This coating agent is used at a pH less than 7. It canalso be gelled by addition of aluminium salts. Gelatine or gum arabicmay also be used as coating agents at a pH of less than 7. Other coatingagents include alginates and guar gum, used in conjunction with anelectrolyte (eg. aluminium chloride or sulphate). The use of coatingagents in multiple emulsions is described in U.S. Pat. No. 4,244,816,the description of which is incorporated herein by reference.

A further ingredient which may be included in the continuous aqueousphase of the multiple emulsions of the invention is a compound whichwill react with and deactivate any of the herbicidal bipyridyliumdiquaternary salt which may diffuse out from or otherwise escape fromthe drops of the first emulsion. Such an ingredient may be termed abipyridylium scavenger. An example of such a compound is the condensateof formaldehyde with the sodium salt of naphthalene-2-sulphonic acidsold under the Trade Name Morwet D425, and having the structure below:##STR3## wherein n ranges from 2 to 9, with an average of 6. Thismaterial will react with, for example, paraquat dichloride to give asalt which is essentially biologically inert, both in a toxicologicaland a herbicidal sense.

The Morwet D425 may be included in the emulsions at a concentration offor example from 12 to 300 grams per liter of the continuous aqueousphase. Other sulphonated or sulphated compounds may also be used asbipyridylium scavengers, for example the disodium salt of chromotropicacid, having the formula: ##STR4## This may be included in the emulsionsat a concentration of 1 to 100 grams per liter of the continuous aqueousphase. Other bipyridylium scavengers include dextran sulphate andsulphated polysaccharides generally.

Other additives whch may be included in the emulsions are Rhodopol MD50(a polysaccharide) at a concentration of, for example, 1-10 grams perliter, alone or combined with Nalfloc (finely divided silica), at aconcentration of for example from 10 to 50 grams per liter of thecontinuous aqueous phase.

In a modification of the process of the invention, the drops of thefirst emulsion may be separated from the aqueous phase by for examplecentrifuging the multiple emulsion. The drops of first emulsion may thenbe redispersed in fresh aqueous phase. This procedure may be useful ifthere is bipyridylium quaternary salt in the aqueous phase which was notentrapped in the oil during the preparation of the multiple emulsion.

Herbicidal bipyridylium quaternary salts which may be used as the activeingredients of the compositions of the invention include those of thefollowing formulae: ##STR5## wherein R¹ and R², which may be the same ordifferent, each stand for an alkyl or alkenyl radical of 1 to 4 carbonatoms, which may be substituted by a hydroxy, carboxy, alkoxy,alkylcarbonyl, alkoxycarbonyl, carbamoyl, of N-alkyl-substitutedcarbamoyl radical, or a halogen atom; [X]^(n-) represents an anion and nis 1, 2, 3 or 4. Preferred alkoxy groups are those containing 1 to 4carbon atoms. Preferred alkylcarbonyl and alkoxycarbonyl groups arethose containing from 2 to 5 carbon atoms. Preferred N-alkyl substitutedcarbamoyl radicals are those in which the N-alkyl substituent orsubstituents contain from 1 to 4 carbon atoms.

Examples of herbicidal bipyridylium diquaternary salts include thoselisted below:

1,1'-ethylene-2,2'-bipyridylium dibromide (diquat dibromide)

1,1'-dimethyl-4,4'-bipyridylium dichloride (paraquat dichloride)

1,1'-dimethyl-4,4'-bipyridylium di(methylsulphate)

1,1'-di-2-hydroxyethyl-4,4'-bipyridylium dichloride

1,1'-bis-3,5-dimethylmorpholinocarbonylmethyl-4,4'-bipyridyliumdichloride (morfamquat dichloride)

1-(2-hydroxyethyl)-1'-methyl-4,4'-bipyridylium dichloride

1,1'-di-carbamoylmethyl-4,4'-bipyridylium dichloride

1,1'-bis-N,N-dimethylcarbamoylmethyl-4,4'-bipyridylium dichloride

1,1'-bis-N,N-diethylcarbamoylmethyl-4,4'-bipyridylium dichloride

1,1'-di-(piperidinocarbonylmethyl)-4,4'-bipyridylium dichloride

1,1'-diacetonyl-4,4'-bipyridylium dichloride

1,1'-diethoxycarbonylmethyl-4,4'-bipyridylium dibromide

1,1'-diallyl-4,4'-bipyridylium dibromide

The names in brackets alongside some of the compounds in the above listare the accepted common names for the cationic portion of the compounds.Thus [paraquat] is the common name for the1,1'-dimethyl-4,4'-bipyridylium cation. Paraquat is a particularlypreferred bipyridylium compound for use in the compositions of theinvention.

Since the herbicidal effect of a bipyridylium quaternary cation isindependent of the nature of the associated anion, the choice of theanion is a matter of convenience, depending, for example, on cost.Preferably the anion is one which gives rise to a salt of convenientwater solubility. Examples of anions, which may be mono- or poly-valent,include acetate, benzenesulphonate, benzoate, bromide, butyrate,chloride, citrate, fluorosilicate, fumarate, fluoroborate, iodide,lactate, malate, maleate, methylsulphate, nitrate, propionate,phosphate, salicylate, succinate, sulphate, thiocyanate, tartrate, andp-toluenesulphonate. The salt of the herbicidal bipyridylium cation maybe formed from a number of similar anions or mixtures of different ones.A salt having any particular desired anion may be prepared either bydirect synthesis from reactants which include the desired anion, or byexchanging the anion of a previously prepared salt of the preferredanion by methods well known in the art, for example by passage of asolution of the previously prepared salt through an ion-exchange resin.For reasons of convenience and economy, the chloride anion is aparticularly preferred anion.

Since the characteristic herbicidal activity of a salt of a herbicidalbipyridylium quaternary cation resides in the cation only, it iscustomary to quote concentrations of active ingredients and rates ofapplication in terms of the amount of bipyridylium quaternary cationused. Application rates and concentrations quoted in this specificationtherefore relate to the amount of bipyridylium quaternary cation unlessotherwise stated.

In another aspect the invention further provides herbicidal compositionsprepared by the process of the invention described above. Theconcentration of bipyridylium diquaternary cation in the compositions ofthe invention is preferably at least 75 grams per liter of thecomposition and more preferably at least 100 grams per liter.Compositions containing 200 grams or more per liter, for example 300grams per liter, may be prepared. Especially high concentrations may beprepared by using super-saturated solutions of bipyridylium salts. Thus,hot saturated solutions of bipyridylium herbicides may be used inpreparing the emulsions. As the emulsion cools, the bipyridyliumherbicide solution becomes super-saturated.

Examples of compositions according to the invention include those inwhich the bipyridylium quaternary salt is paraquat dichloride and thosein which the bipyridylium quaternary salt comprises a mixture of equalamounts of paraquat dichloride and diquat dibromide (calculated onbipyridylium cation basis).

The amount of the first emulsifier may be for example from 10 to 100grams per liter, preferably 40 to 75 grams per liter of the firstemulsion. The amount of the second emulsifier may be from 5 to 100 gramsper liter, preferably 10 to 50 grams per liter of the continuous aqueousphase.

It will be evident that a composition containing a particularconcentration of bipyridylium diquaternary salt may be prepared indifferent ways, by using different concentrations of aqueousbipyridylium salt solution in combination with different amounts of oil.In the Examples, the proportions of ingredients have been quoted interms of volume fractions F1 and F2 where F1 is the ratio of the volumeof bipyridylium diquaternary salt solution to the total volume of thefirst emulsion, and F2 is the ratio of the volume of first emulsion tothe total volume of the finished formulation. The compositions of theinvention may also comprise ingredients which have previously beenproposed to reduce the hazards associated with the possibility ofaccidental swallowing of herbicidal bipyridylium diquaternary salts.Thus for example the compositions may contain an emetic, for example anemetic of the class disclosed in U.K. Pat. No. 1507407. A preferredemetic of this class is2-amino-6-methyl-5-oxo-4-1-propyl-4,5-dihydro-s-triazolo[1,5-a]-pyrimidinewhich may be incorporated in the composition in the proportion of forexample from 0.25 to 2.0 parts by weight per 100 parts of herbicidalbipyridylium diquaternary cation. The composition may also contain acolouring agent, for example a blue pigment (eg. the pigment sold underthe trade name Monastral Blue). The compositions may also contain anodourant as a warning. Examples of odourants include pyridine base (seeU.K. Pat. No. 1406881), valeric acid, and tetrahydrothiophene. Pyridinebase may be included at a concentrated of, for example, 5 to 20 gramsper liter of the composition.

An assessment of the effectiveness with which the bipyridyliumdiquaternary salt is retained within the drops of the emulsion may begained by physical techniques. Thus, dialysis of a sample of thecomposition followed by analysis of the dialysate gives a value for theamount of bipyridylium diquaternary salt which has leaked out of thedrops during the period of dialysis, plus the amount of the bipyridyliumdiquaternary salt which was not entrapped in the drops during thepreparation of the composition. By centrifuging a sample of thecomposition, the continuous aqueous phase may be separated from thedrops containing the dispersed droplets of aqueous bipyridyliumdiquaternary salt solution. Analysis of the separated continuous aqueousphase then gives a value for the amount of bipyridylium diquaternarysalt which escaped entrapment in the drops during the preparation of thecomposition. Subtraction of this value from the value obtained from thedialysis procedure gives the amount of bipyridylium diquaternary saltwhich leaked out from the drops during the period of dialysis (24hours). The amount of bipyridylium diquaternary salt which was found tohave leaked out of the drops during the dialysis period ranged from0.16% in the case of composition no 3 in Table I to 16.1% in the case ofcomposition no 5, these percentages being based on the amount ofbipyridylium salt originally present in the drops. Even at the highervalue, more than 80% of the bipyridylium salt was retained within thedrops. Applying the results of this in vitro test to the case where aquantity of the composition had been accidentally swallowed, this wouldmean that even in the least effective composition, less than 20% of theingested bipyridylium quaternary salt would be available for absorptionthrough the gastro-intestinal tract, an effective reduction of more than80% in the amount of material potentially available to exert deleteriouseffects.

In laboratory tests with compositions according to the inventioncontaining paraquat as the bipyridylium herbicide, there was at least atwo-fold reduction in oral toxicity to rats as compared with an aqueousformulation of paraquat. In dogs, a reduction in oral toxicity of up tosix-fold was observed.

The following Examples illustrate the preparation of multiple emulsionsby the process of the invention.

EXAMPLE 1

The procedure followed for preparing the multiple emulsions was asfollows.

The first emulsifier was dissolved in the oil with heating, and thesolution allowed to cool. The amount of emulsifier used was from 50 to100 grams per liter of the oil. A solution of paraquat dichloride inwater (300 grams per liter) was added gradually to the oil/emulsifierover a period of about two minutes, with stirring by an Elado stirrer atsetting 4 (on a 1-10 scale). The stirring speed was then increased tosetting 6 to 7 for 10 minutes. In the resulting emulsion, the waterphase occupied 65% of the volume of the emulsion.

This first emulsion was diluted with oil (30% of the volume of theemulsion) and then added slowly with stirring to a solution of sodiumchloride in water (1.61 Molar) containing Surfactant C (from 5 to 15grams per liter). Stirring was by an ordinary paddle stirrer and wascontinued for one hour. In an alternative procedure, the first emulsionafter dilution with oil, was added quickly to the sodium chloridesolution and stirred for 30 seconds only with an Elado stirrer at a lowspeed setting (ca 2.6). The final multiple emulsion obtained by eitherof these two procedures contained 50% by volume of the first emulsiondiluted with oil.

The above procedure was carried out using the combinations ofemulsifiers and oils shown in Table I below.

                                      TABLE I                                     __________________________________________________________________________           First Emulsifier                                                                             Concentration of                                                                        Type of                                              & concentration                                                                              second emulsifier                                                                       stirring in                                   Composition                                                                          in first       (Surfactant C) in                                                                       secondary                                     No     emulsion Oil   aqueous phase                                                                           emulsification                                __________________________________________________________________________    1      Surfactant A                                                                           Isopar M                                                                            10 g/liter                                                                              Paddle                                               at 50 g/liter            stirring                                      2      Surfactant A                                                                           Isopar M                                                                            10 g/liter                                                                              Paddle                                               at 100 g/liter           stirring                                      3      Surfactant A/                                                                          Isopar M                                                                             5 g/liter                                                                              Paddle                                               Surfactant D             stirring                                             1:1 mixture at                                                                50 g/liter                                                             __________________________________________________________________________

By repeating the preparation of the above compositions 1 to 6 using anaqueous solution of paraquat dichloride containing 376 instead of 300grams of paraquat per liter, and a 2-molar solution of sodium chloridein place of the 1.61 molar solution, a series of compositionscorresponding to those of Table 1 was obtained, in which the firstemulsion contained 245 grams per liter of paraquat and the finalmultiple emulsion contained 94 grams per liter of paraquat, comparedwith 195 grams per liter and 75 grams per liter respectively for thecompositions prepared as above.

EXAMPLE 2

This Example illustrates further compositions prepared according to theinvention.

Further multiple emulsion compositions were prepared following theprocedure described in Example 1. In each case a solution of paraquatdichloride containing 376 grams of paraquat per liter was used asstarting material. The first emulsion was diluted with further oil so asto give a paraquat concentration in the multiple emulsion compositionfinally obtained of 100 grams per liter. The second emulsifier used wasSurfactant C in each case, at a concentration of 10 grams per literthroughout. In each case the secondary emulsification was carried out bypaddle stirring. The compositions prepared are listed in Table 2 below:

                  TABLE 2                                                         ______________________________________                                                   First emulsifier and                                               Composition                                                                              concentration in first                                             No.        emulsion        Oil                                                ______________________________________                                        7          Surfactant D    White oil                                                     50 g/liter                                                         8          Surfactant D    Diesel oil                                                    50 g/liter                                                         9          Surfactant D    Isopar M and                                                  50 g/liter      liquid paraffin                                                               1:1 mixture                                        10         Surfactant B    White oil                                                     50 g/liter                                                         11         Surfactant B    Diesel oil                                                    50 g/liter                                                         12         Surfactant B    Liquid paraffin                                               50 g/liter                                                         13         Surfactant A    Isopar M and                                                  50 g/liter      liquid paraffin                                                               3:7 mixture                                        14         Surfactant D    Isopar M and                                                  50 g/liter      diesel oil 1:1                                                                mixture                                            15         Surfactant D    Isopar M and                                                  50 g/liter      Solvesso 100 95:5                                                             mixture                                            ______________________________________                                    

EXAMPLE 3

This Example illustrates further compositions prepared according to theinvention. The procedure described in Example 1 was followed, exceptthat the first emulsion was not diluted by adding oil. The proportionsof the ingredients used were selected to give a concentration ofparaquat in the final multiple emulsion composition of 100 grams perliter. Secondary emulsification was by paddle stirring in each case. Theproportions in which the oil and aqueous phases are mixed is given bythe volume fractions F₁ and F₂. Thus a value of F₁ of 0.65 means thatthe paraquat solution was mixed with oil to form the first emulsion inthe ratio of 0.65 parts by volume of aqueous solution to 0.35 parts ofoil while a value of 0.43 for F₂ means that 0.43 parts by volume of thefirst emulsion was mixed with 0.57 parts of the continuous aqueous phaseto form the final multiple emulsion composition. The compositionsprepared are listed in Table 3 below.

                                      TABLE 3                                     __________________________________________________________________________                         Electrolyte and                                                               concentration. Second                                           First emulsifier                                                                            emulsifier and                                                                           Paraquat                                             and concentration                                                                           concentration                                                                            concentration                                 Composition                                                                          in first emulsion                                                                           (grams per liter)                                                                        g/liter and volume                            No.    in grams per liter                                                                     Oil  in aqueous phase                                                                         fractions used                                __________________________________________________________________________    16     Span 80  Isopar M                                                                           NaCl 1.4 M 376                                                  50 g/l        Tween 20 5 g/l                                                                           F.sub.1 = 0.65                                                                F.sub.2 = 0.43                                17     Arlacel 83:                                                                            Isopar M                                                                           NaCl 1.4 M 376                                                  lecithin 7:3  10 g/l Tween 20                                                                          F.sub.1 = 0.65                                       mixture 50 g/l                                                                              10 g/l Surfactant C                                                                      F.sub.2 = 0.43                                18     Arlacel 83:                                                                            Isopar M                                                                           NaCl 1.4 M 376                                                  lecithin 7:3  10 g/l Tween 20                                                                          F.sub.1 = 0.65                                       mixture 75 g/l                                                                              10 g/l Surfactant C                                                                      F.sub.2 = 0.43                                __________________________________________________________________________

EXAMPLE 4

This Example illustrates further compositions prepared according to theinvention. The procedure was as described in Example 3. The compositionsprepared are listed in Table 4 below.

                                      TABLE 4                                     __________________________________________________________________________                        Electrolyte and                                                               concentration. Second                                            First emulsifier                                                                           emulsifier and                                                                           Paraquat                                              and concentration                                                                          concentration                                                                            concentration                                  Composition                                                                          in first emulsion                                                                          (grams/liter)                                                                            and volume fractions                           No.    in grams per liter                                                                     Oil in aqueous phase                                                                         used                                           __________________________________________________________________________    29     Surfactant D                                                                           Diesel                                                                            NaCl 2 M   376                                                   50 g/l       Surfactant C 10 g/l                                                                      F.sub.1 = 0.65                                                     Tween 20 10 g/l                                                                          F.sub.2 = 0.5                                  30     Surfactant D                                                                           Diesel                                                                            NaCl 2 M   376                                                   50 g/l       Surfactant C 10 g/l                                                                      F.sub.1 = 0.65                                                     Tween 20 50 g/l                                                                          F.sub.2 = 0.5                                  31     Surfactant D                                                                           Diesel                                                                            NaCl 2 M   376                                                   50 g/l       Surfactant E 10 g/l                                                                      F.sub.1 = 0.65                                                                F.sub.2 = 0.5                                  32     Surfactant D                                                                           Diesel                                                                            NaCl 2 M   376                                                   50 g/l       Surfactant F 10 g/l                                                                      F.sub.1 = 0.65                                                                F.sub.2 =0.5                                   __________________________________________________________________________

EXAMPLE 5

This Example illustrates further compositions prepared according to theinvention containing further ingredients to improve the retention of theherbicidal bipyridylium diquaternary salt within the drops of the firstemulsion. The compositions were prepared according to the proceduredescribed in Example 3. The further ingredient(s) may be added to theaqueous solution of the bipyridylium salt or in the oil before theemulsifying process is begun. In the examples of compositions listed inTable 5 below, the bipyridylium quaternary salt used is paraquatdichloride throughout, and the concentration used was 376 grams perliter in the solution used to make the first emulsion. The volumefractions F₁ and F₂ were 0.65 and 0.50 respectively throughout, and theconcentration of sodium chloride in the continuous aqueous phase was 2Mexcept where indicated in the Table. The abbreviation CMC stands forcarboxymethyl cellulose. Aluminium ion was added as aluminium sulphatehexahydrate. In some cases citric acid was added and the molar ratio ofacid to aluminium ion is given in the Table.

                                      TABLE 5                                     __________________________________________________________________________    Composition                                                                          First emulsifier        Second emulsifier                              No.    (grams/liter)                                                                         Oil  Additive (grams/liter)                                                                   (grams/liter)                                  __________________________________________________________________________    52     Surfactant A                                                                          Isopar M                                                                           CMC F20P   Surfactant C                                          50 g/l       10 g/l     10 g/l                                                             CMC: Al.sup.3+                                                                70:1 mole ratio                                                               and citric acid:Al                                                            6:1 mole ratio                                            53     Surfactant A                                                                          Isopar M                                                                           CMC F20P   Surfactant C                                          50 g/l       50 g/l     10 g/l                                                             CMC:Al.sup.3+                                                                 mole ratio 350:1                                                              and citric acid:Al.sup.3+                                                     mole ratio 6:1                                            54     Surfactant D                                                                          Isopar M                                                                           CMC F20P   Surfactant C                                          50 g/l       10 g/l     10 g/l                                         __________________________________________________________________________

EXAMPLE 6

This Example illustrates further compositions prepared according to theinvention. The compositions were prepared according to the proceduredescribed in Example 3. In the examples of compositions listed in Table6 below, the bipyridylium quaternary salt used is paraquat dichloridethroughout, and is concentration was 376 grams per liter in the solutionused to make the first emulsion. The volume fractions F1 and F2 were0.65 and 0.50 respectively throughout, and the concentrations of sodiumchloride in the continuous aqueous phase was 2M.

                                      TABLE 6                                     __________________________________________________________________________    Composition                                                                          First emulsifier        Second emulsifier                              No.    (grams/liter)                                                                         Oil  Additive (grams/liter)                                                                   (grams/liter)                                  __________________________________________________________________________    76     Surfactant A                                                                          Isopar M                                                                           --         Surfactant C                                          25 g/l                  10 g/l                                         77     Surfactant A                                                                          Isopar M                                                                           --         Surfactant C                                          50 g/l                  10 g/l                                         78     Surfactant A                                                                          Isopar M                                                                           --         Surfactant C                                          75 g/l                  10 g/l                                         79     Surfactant A                                                                          Isopar M                                                                           --         Surfactant C                                          100 g/l                 10 g/l                                          80(a) Surfactant A                                                                          Isopar M                                                                           --         Surfactant C                                          50 g/l                  10 g/l                                         81     Surfactant A                                                                          Isopar M                                                                           Morwet D425                                                                              Surfactant C                                          50 g/l       10 g/l     10 g/l                                         __________________________________________________________________________

EXAMPLE 7

This Example illustrates further compositions prepared according to theinvention. The procedure used was that described in Example 3. Thebipyridylium quaternary salt used was paraquat dichloride throughout, ata concentration of 376 grams per liter in the solution used to make thefirst emulsion. The volume fractions F1 and F2 were 0.65 and 0.50respectively throughout, and the electrolyte was sodium chloride.

                                      TABLE 7                                     __________________________________________________________________________    Composition                                                                          First emulsifier                                                                           Second emulsifier                                                                      Concentrations                                   No.    (grams/liter)                                                                         Oil  (grams/liter)                                                                          of sodium chloride                               __________________________________________________________________________    100    Surfactant D                                                                          Diesel oil                                                                         Surfactant F                                                                           2 M                                                     25 g/l       10 g/l                                                    101    Surfactant D                                                                          Diesel oil                                                                         Surfactant C                                                                           3 M                                                     50 g/l       10 g/l                                                    102    Surfactant D                                                                          Diesel oil                                                                         Surfactant F                                                                           2 M                                                     50 g/l       20 g/l                                                    103    Surfactant D                                                                          Diesel oil                                                                         Surfactant C                                                                           2 M                                                     30 g/l       10 g/l                                                    104    Surfactant D                                                                          Diesel oil                                                                         Surfactant C                                                                           2 M                                                     40 g/l       10 g/l                                                    105    Surfactant D                                                                          Diesel oil                                                                         Surfactant C                                                                           2 M                                                     50 g/l       20 g/l                                                    __________________________________________________________________________

EXAMPLE 8

This Example illustrates the herbicidal activity of an emulsionaccording to the invention in which the herbicidal bipyridyliumquaternary salt is paraquat dichloride. Appropriate quantities of theemulsion to give the application rates specified in the table below werediluted with water to a spray volume equivalent to 200 liters perhectare and sprayed on to four-week old test plants grown in aglass-house in 3-inch (ca. 7.6 cm) diameter pots. For comparison, acommercially used formulation of paraquat dichloride sold under theTrade Mark "Gramoxone" 100 comprising an aqueous solution of paraquatdichloride together with a mixture of surface-active agents wassimilarly diluted and applied to the test plants. Three replicates ofeach species of test plant were used. Seven days after application, thedamage to the test plants was assessed on a scale of 0 to 10 where 0denotes no damage and 10 complete kill, and averaged for the threereplicates. The results are given in Table 8.

                  TABLE 8                                                         ______________________________________                                                Rate of                                                                       application                                                                   of paraquat                                                                   (grams per                                                                              Test Plants                                                 Treatment hectare)    GA     TO     AG   LL                                   ______________________________________                                        "Gramoxone"                                                                             200         3.3    6.7    6.7  8.0                                  100       300         --     8.3    8.3  8.7                                            400         7.7    8.0    8.3  9.0                                            800         8.0    --     --   --                                   Composition                                                                             200         3.3    7.7    6.7  9.0                                  37        300         --     8.3    8.3  9.0                                            400         8.0    9.0    8.3  8.7                                            800         8.3    --     --   --                                   ______________________________________                                    

The names of the test plants are as follows:

GA Galium aparine

TO Tomato (variety Ailsa Craig)

LL Lolium perenne

AG Agropyron repens

I claim:
 1. A concentrated herbicidal composition comprising 75 grams ormore per liter of a herbicidal bipyridylium diquaternary salt of theformula: ##STR6## wherein R1 and R2, which may be the same or differenteach stand for an alkyl or alkanyl radical of 1 to 4 carbon atoms, whichmay be substituted by a hydroxy, carboxy, alkoxy, alkylcarbonyl,alkoxycarbonyl, carbamoyl or N-alkyl-substituted carbamoyl radical or ahalogen atom; [X]^(n-) represents an anion and n is 1, 2, 3 or 4; thesaid composition having a reduced oral toxicity towards mammals ascompared with compositions consisting of a concentrated aqueous solutionof a herbicidal bipyridylium diquaternary salt, the said compositionsbeing prepared by a process comprising as a first step agitating anaqueous solution of a herbicidal bipyridylium diquaternary salt with anoil and a first emulsifier having a low HLB value to give a firstemulsion comprising droplets of herbicidal bipyridylium diquaternarysalt solution dispersed in a continuous oil phase, and as a second step,agitating the first emulsion with water and a second emulsifier having ahigh HLB value to give a second emulsion comprising drops of the firstemulsion dispersed in a continuous aqueous phase, and wherein the waterused to prepare the second emulsion contains a solute in sufficientconcentration to bring the continuous aqueous phase into substantialosmotic balance with the aqueous solution of the herbicidal bipyridyliumdiquaternary salt.
 2. A composition as claimed in claim 1 wherein theherbicidal bipyridylium diquaternary salt is a salt of the1,1'-dimethyl-4,4'-bipyridylium ion.
 3. A composition as claimed inclaim 1 or claim 2 wherein the solute is sodium chloride.
 4. Acomposition as claimed in any of claims 1, 3 or 2 3 wherein the oilcomprises diesel oil or Isopar M or mixtures thereof.
 5. A compositionas claimed in any of claims 1, 3, 4, or 2 4 wherein the emulsifier oflow HLB value comprises a block co-polymer of poly-12-hydroxy stearicacid and polyethylene oxide; a reaction product ofpolyisobutylenesuccinic anhydride and ethanolamine having the formula:##STR7## having a molecular weight in the range 400 to 5000; or acompound of the last foregoing formula reacted with a molar proportionof phosphoric acid to yield the monophosphate derivative.
 6. Acomposition as claimed in any of claims 1, 3, 4, 5 or 2 5 wherein theemulsifier of high HLB value comprises a condensate of p-nonylphenolwith propylene oxide and ethylene oxide and having the followingformula: ##STR8## wherein x may be from 2 to 50 and y may be from 10 to100, or sorbitan monolaurate condensed with 20 molar proportions ofethylene oxide.
 7. A composition as claimed in any of claims 3, 4, 5, 6or 2 6 wherein the emulsion comprises one or more further ingredients toimprove the retention of the herbicidal bipyridylium diquaternary saltwithin the droplets dispersed in the continuous oil phase, suchingredients comprising polyisobutene; sodium carboxymethyl cellulose inconjunction with an alkyltrimethylammonium salt or a polyvalent cation;xanthan gum in conjunction with a polyvalent cation or a borate salt;gum arabic; guar gum; gelatine; or sodium polymethylmethacrylatecondensed with ethylene oxide.